The identity and topographic localization of immunocompetent cells and the alteration of surface markers on ocular resident cells in animals with various experimental uveitis were analyzed by immunohistochemical studies and in situ hybridization. Previously, we demonstrated that T lymphocytes were the predominantly infiltrating cells in experimental autoimmune uveoretinitis (EAU) and experimental melanin-protein-induced uveitis (EMIU), yet both macrophages and polymorphonuclear neutrophils were the predominantly infiltrating cells in endotoxin-induced uveitis (EIU). Cytokines (e.g., interleukins), inflammatory mediators (e.g., nitric oxide), and retinal proteins (e.g., S-antigen (S-Ag)) play an important role in the immunopathogenesis of uveitic models. Agents such as FK506 and rapamycin that modulate cytokines and T-cell receptors can alter the immunopathology of the experimental model. We studied the susceptibility and genetic control of EIU in mice. New animal models, including those for EMIU, experimental blepharitis, murine allergic conjunctivitis, and murine toxoplasmosis, have been developed and studied. The characteristic of recurrences in EMIU closely resembles endogenous uveitis in humans. Experimental blepharitis in the mouse induced by immunization of human monoclonal antibody of Id16/6 resembles human blepharitis and is a major histocompatibility complex (MHC) class I-dependent disease. Murine allergic conjunctivitis induced by compound 48/80 mimics allergic conjunctivitis and helps us to evaluate anti-allergic medications. Murine toxoplasmosis infected with Toxoplasma gondii resembles acquired ocular toxoplasmosis, and nitric oxide (NO) plays an important role in the infection. Specimens from human ocular tissues with uveitis, retinal and corneal diseases, tumors, and metabolic genetic disorders are studied using routinehistological, immunohistochemical, and in situ hybridization techniques. In uveitis, immunocompetent cells and lymphokines besides the stimulators (e.g., infectious organisms) are valuable adjuncts to the clinical diagnosis and the understanding of pathogenesis of the diseases. Aggressive treatment for sympathetic ophthalmia is needed. In nonuveitic conditions, detection of cytokines (e.g., interleukin-10 (IL-10) in intraocular lymphoma) may assist the diagnosis in these diseases. Elucidating the immunopathological role of the relationships between infiltrating inflammatory or malignant cells and the resident cells in the clinical behavior of various diseases will increase our understanding of human ocular disorders and provide better treatment.